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Introduction Timely diagnosis, etiopathogenesis, treatment and prevention of the progression of pediatric flexible pes planovalgus (FPPV) are essential to prevent irreversible complications. The objective was to determine a correlation between whole-blood serotonin level and flexible pes planovalgus in children and adolescents over a period of four years with progression of the condition. Material and methods The whole-blood serotonin level was measured in children and adolescents aged 5-15 years with FPPV and compared with data from photoplantograms, a pronation angle of the calcaneus and radiographs of the feet. Based on serotonin measurements and photoplantograms, two groups were identified according to the course of flexible pes planovalgus and measurements during the next four years. Results Normal serotonin levels were maintained in the non-progressive FPPV group throughout the study with a 9.2 % decrease in the pronation of the calcaneus at 4 years. Progressive FPPV patients showed higher serum serotonin at one year with a 38.3 % increase at 4 years, increased pronation of the calcaneus by 21.2% and radiologically decreased height of the arch by 18.7 %. A moderate correlation between whole-blood serotonin levels, pronation of the calcaneus and the height of the foot arch was radiologically revealed in patients with a different course of FPPV. Analysis of the diagnostic effectiveness of the whole-blood serotonin test in patients with FPPV showed high sensitivity and specificity in predicting the risk of progression of FPPV. Discussion Literature review showed a paucity of research on clinical and laboratory detection of the progression of FPPV and examination of neurotransmitter mechanisms in the foot pathology. Plantography, 3D scanning and radiography were the main methods for the diagnosis of the flat feet. Conclusion The correlation between whole-blood serotonin level and flexible pes planovalgus in children and adolescents was identified and suggested involvement of the serotoninergic system in the formation and progression of foot pathology.